Trelstar Depot

"The U.S. Food and Drug Administration today expanded the approved use of Zytiga (abiraterone acetate) to treat men with late-stage (metastatic) castration-resistant prostate cancer prior to receiving chemotherapy.

Trelstar Depot

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse
reaction rates observed in the clinical trials of a drug cannot be directly
compared with rates in the clinical trials of another drug and may not reflect
the rates observed in practice.

The safety of the three TRELSTAR formulations was evaluated in clinical trials
involving patients with advanced prostate cancer. Mean testosterone levels increased
above baseline during the first week following the initial injection, declining
thereafter to baseline levels or below by the end of the second week of treatment.
The transient increase in testosterone levels may be associated with temporary
worsening of disease signs and symptoms, including bone pain, neuropathy, hematuria,
and urethral or bladder outlet obstruction. Isolated cases of spinal cord compression
with weakness or paralysis of the lower extremities have occurred [see WARNINGS
AND PRECAUTIONS].

Adverse reactions reported for each of the three TRELSTAR formulations in the
clinical trials, are presented in Table 2, Table 3, and Table 4. Often, causality
is difficult to assess in patients with metastatic prostate cancer. The majority
of adverse reactions related to triptorelin are a result of its pharmacological
action, i.e., the induced variation in serum testosterone levels, either an
increase in testosterone at the initiation of treatment, or a decrease in testosterone
once castration is achieved. Local reactions at the injection site or allergic
reactions may occur.

The following adverse reactions were reported to have a possible or probable
relationship to therapy as ascribed by the treating physician in at least 1%
of patients receiving TRELSTAR 3.75 mg.

1 Adverse reactions for TRELSTAR
11.25 mg are coded using the WHO Adverse Reactions Terminology (WHOART)

The following adverse reactions occurred in at least 5% of patients receiving
TRELSTAR 22.5 mg. The table includes all reactions whether or not they were
ascribed to TRELSTAR by the treating physician. The table also includes the incidence of these adverse reactions that were considered by the treating physician
to have a reasonable causal relationship or for which the relationship could
not be assessed.

Table 4: TRELSTAR 22.5 mg: Adverse Reactions Reported by
5% or More of Patients During Treatment

Adverse Reactions1

TRELSTAR 22.5 mg N =120

Treatment-Emergent

Treatment-Related

N

%

N

%

General Disorders and Administration Site Conditions

Edema peripheral

6

5.0

0

0

Infections and Infestations

Influenza

19

15.8

0

0

Bronchitis

6

5.0

0

0

Endocrine

Diabetes Mellitus/Hyperglycemia

6

5.0

0

0

Musculoskeletal and Connective Tissue Disorders

Back pain

13

10.8

1

0.8

Arthralgia

9

7.5

1

0.8

Pain in extremity

9

7.5

1

0.8

Nervous System Disorders

Headache

9

7.5

2

1.7

Psychiatric Disorders

Insomnia

6

5.0

1

0.8

Renal and Urinary Disorders

Urinary tract infection

14

11.6

0

0

Urinary retention

6

5.0

0

0

Reproductive System and Breast Disorders

Erectile dysfunction

12

10.0

12

10.0

Testicular atrophy

9

7.5

9

7.5

Vascular Disorders

Hot flush

87

72.5

86

71.7

Hypertension

17

14.2

1

0.8

1Adverse reactions for TRELSTAR
22.5 mg are coded using the Medical Dictionary for Regulatory Activities
(MedDRA).

Changes in Laboratory Values During Treatment

The following abnormalities in laboratory values not present at baseline were
observed in 10% or more of patients:

TRELSTAR 3.75 mg: There were no clinically meaningful changes in laboratory
values detected during therapy.

TRELSTAR 22.5 mg: Decreased hemoglobin and increased glucose and hepatic
transaminases were detected during the study. The majority of the changes were
mild to moderate.

Postmarketing Experience

The following adverse reactions have been identified during post approval use
of gonadotropin releasing hormone agonists. Because these reactions are reported
voluntarily from a population of uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal relationship to drug
exposure.

During postmarketing surveillance, rare cases of pituitary apoplexy (a clinical
syndrome secondary to infarction of the pituitary gland) have been reported
after the administration of gonadotropin-releasing hormone agonists. In a majority
of these cases, a pituitary adenoma was diagnosed with a majority of pituitary
apoplexy cases occurring within 2 weeks of the first dose, and some within the
first hour. In these cases, pituitary apoplexy has presented as sudden headache,
vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes
cardiovascular collapse. Immediate medical attention has been required.

DRUG INTERACTIONS

No drug-drug interaction studies involving triptorelin have been conducted.

Human pharmacokinetic data with triptorelin suggest that C-terminal fragments
produced by tissue degradation are either degraded completely within tissues
or are rapidly degraded further in plasma, or cleared by the kidneys. Therefore,
hepatic microsomal enzymes are unlikely to be involved in triptorelin metabolism.
However, in the absence of relevant data and as a precaution, hyperprolactinemic
drugs should not be used concomitantly with triptorelin since hyperprolactinemia
reduces the number of pituitary GnRH receptors.